AB0161 THE RELATIONSHIP OF TRYPTOPHAN CATABOLISM WITH RHEUMATOİD ARTHRITIS DİSEASE ACTİVİTY ABSTRACT
Authors: A. Kor, S. Erten, E. F. Yurt, I. Dogan, H. Apaydin, M. A. Serdar, C. Bİçer
Journal: Annals of the Rheumatic Diseases (2022)

Background Tryptophan (Trp) is an essential amino acid. The immunosuppressive effect caused by Kynurenine (Kyn) and its metabolites formed by the catabolism of Trp is thought to be an important physiological mechanism. Objectives This study aims to evaluate the relationship of Kyn and its metabolites formed in Trp catabolism with rheumatoid arthritis (RA) disease activation and to investigate the usability of these markers in the diagnosis and treatment of RA. Methods 50 RA patients followed in our rheumatology clinic and 41 healthy controls without chronic disease were included in this study. Disease Activity Score 28 (DAS28) was used to evaluate the association of Kyn metabolites and Indolamine 2,3 dioxygenase (IDO) enzyme activity with RA disease activity. The task of this enzyme is to provide Kyn formation with Trp catabolism. Results In this study, lower Trp levels were found in the RA group compared to the control group (11285.47±2318.93-13320.31±3771.27, respectively) compared to the Trp mean (p&lt;0.01). In terms of the Kyn/Trp ratio, a significantly higher Kyn/Trp ratio (4.42±1.77-3.27±0.71, respectively) was found in the RA compared to the control group (p&lt;0.001). There was no significant difference between the study groups in terms of Kyn averages (p&gt;0.05). A significant correlation was found between Trp levels and morning stiffness (r: -0.321, p&lt;0.05) and the DAS28 score (r:-0.566, p&lt;0.01). A significant positive correlation was found between the Kyn/Trp ratio and C-reactive protein (r:0.317, p&lt;0.05), sedimentation (r:0.319, p&lt;0.05), morning stiffness (r:0.287, p&lt;0.05) and DAS28 score (r:0.322, p&lt;0.01). Table 1. Comparison of study parameters between RA and control group. Parameter Rheumatoid arthritis Control group P-Value Tryptophan (ng/ml) 11285,47±2318,93 13320,31±3771,27 &lt;0.01 Kynurenine (ng/ml) 477,68±158,38 437,51±162,10 &gt;0.05 Kyn/Trp ratio 4,42±1,77 3,27±0,71 &lt;0.001 All values were expressed as mean ± SD. All values were calculated using independent sample t-test for normal distribution. Figure 1. Correlation relationship between DAS 28 and Trp levels (r: -0,321, p &lt; 0.01) Conclusion In this study, we observed that RA has a significant relationship with Trp levels and Kyn/Trp ratio. In addition to the literature, we found that RA activation indicator DAS28 score and Kyn/Trp ratio and Trp level showed a statistically significant correlation. Our study has shown that the Trp catabolic pathway can be an important field of study for more effective and safe treatment of RA. References [1]Smolen JS, Aletaha D, Barton A, Burmester G, Emery P, et al. Rheumatoid arthritis. Nat Rev Dis Primers. 2018;4:18001. doi:10.1038/nrdp.2018.1 [2]Choy EH, Panayi GS. Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med [3]Murray PJ. Amino acid auxotrophy as a system of immunological control nodes. Nature immunology, 2016;17.2: 132-139. doi:10.1038/ni.3323 [4]Frumento G, Rotondo R, Tonetti M, Damonte G, Benatti U, et al. Tryptophan-derived catabolites are [5]De Jong RA, Nijman HW, Boezen HM, Volmer M, Ten Hoor KA, et al. Serum tryptophan and kynurenine concentrations as parameters for indoleamine 2, 3-dioxygenase activity in patients with endometrial, ovarian, and vulvar cancer. International Journal of Gynecologic Cancer, 2011;21.7. doi:10.1097/IGC.0b013e31822017fb [6]Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT., et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis &amp; Rheumatism, 2010;62.9:2569-2581. doi:10.1002/art.27584. [7]Ozkan Y, Mete G, Sepici-Dincel A, Sepici V, Simsek B. Tryptophan degradation and neopterin levels in treated rheumatoid arthritis patients. Clinical rheumatology; 2012;31.1:29-34. doi:10.1007/s10067-011-1767-5 Trp: Tryptophan, DAS28: Disease Activity Score Acknowledgements This study was supported by the Scientific and Technological Research Council of Turkey (TUBITAK). The authors thank TUBITAK for its financial support Disclosure of Interests None declared